anti-Myeloid/lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog, Drosophila), Translocated To, 3 (MLLT3) Antibodies

Human Myeloid/lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog, Drosophila), Translocated To, 3 (MLLT3) interaction partners

1. This system provides for rapid systematic screening of relative risk, dose dependence, and combinatorial impact of multitudes of dietary and environmental exposures on MLL-AF9 translocations

2. miR-564 inhibited metastasis and proliferation of prostate cancer by targeting MLLT3

3. MLL-AF9 fusion is associated with acute myeloid leukemia.

4. Structural insights into H3 histone crotonyl-lysine recognition by the AF9 YEATS domain have been presented.

5. A luciferase reporter gene assay revealed that hsp70 promoter activation is enhanced by the transcriptional co-activator AF9 and splicing mediator SNRPE, but suppressed by the coiled-coil domain-containing protein CCDC127.

6. YEATS domain of AF9 directly links histone crotonylation to active transcription.

7. Results show that human MLL-AF9 expression in mouse long-term hematopoietic stem cells causes invasive, chemoresistant acute myeloid leukemia that expresses genes related to epithelial-mesenchymal transition.

8. Results show that MLL-AF9 reduces Id2 and increases E2-2 expression to drive and sustain leukemia stem cell potential in MLL-rearranged acute myeloid leukemia (AML). Low expression of Id2 or of an Id2 gene signature is associated with poor prognosis in not only MLL-rearranged but also t(8;21) AML patients.

9. Exploring the mechanism how AF9 recognizes and binds H3K9ac by molecular dynamics simulations and free energy calculations.

10. Studies identified the evolutionarily conserved Af9 YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control.

11. AF9 and its homolog ENL directly interact with AF4.

12. Abrogation of Rac1 signaling causes DNA double-strand breaks in acute monocytic leukemia cells harbouring the MLL-AF9 oncogene.

13. Interaction with CBX8 precludes AF9-DOT1L binding.

14. We demonstrate that leukemogenic activity of MLL-AF9 requires RUVBL2 (RuvB-like 2), an AAA+ ATPase family member that functions in a wide range of cellular processes, including chromatin remodeling and transcriptional regulation.

15. neonatal cells expressing MLL-AF9 were enriched for gene signatures associated with poor prognosis

16. AF9 functions as a signaling hub that regulates transcription through dynamic recruitment of cofactors in normal hematopoiesis and in acute leukemia.

17. Identification of genes that define transcription factor networks and important genetic pathways acting during progression of leukemia induced by MLL fusion oncogenes.

18. we identified a novel fusion gene consisted of PAX5 and MLLT3 during progression from chronic phase to blastic phase in chronic myeloid leukemia

19. MLL-AF9-negative U937 cells but not positive MLL-AF9 THP-1 cells, suggesting that the toxocity ting was not antibody-mediated by antibodies against MLL-AF9 protein.

20. Within the group of MLL-AF9-positive patients, high BRE expression predicted superior survival, while normal BRE expression predicted extremely poor survival.

Mouse (Murine) Myeloid/lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog, Drosophila), Translocated To, 3 (MLLT3) interaction partners

1. Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model.

2. YEATS domain of AF9 directly links histone crotonylation to active transcription.

3. Data suggest that RAS-homolog enriched in brain protein (Rheb1) promotes MLL-AF9 fusion protein initiated acute myeloid leukemia (AML) progression through target of rapamycin complex 1 (mTORC1) signaling pathway.

4. Using a PDK1 conditional deletion MLL-AF9 murine AML model, we revealed that the deletion of PDK1 prolonged the survival of AML mice by inducing LSC apoptosis

5. define a specific pairing of two amino acids that creates a salt bridge between MLLT1/3 and AFF proteins that is critically important for MLL-mediated transformation of HPCs

6. Af9 mediates site-selective physical and functional recruitment of Rnf2 to the alpha-ENaC promoter to constrain basal alpha-ENaC transcription in collecting duct cells.

7. Impaired alphaENaC expression due to failure to inhibit Dot1a-Af9 may play an important role in the early stages of pseudohypoaldosteronism type 1 in MR(-/-) mice.

8. We demonstrate that leukemogenic activity of MLL-AF9 requires RUVBL2 (RuvB-like 2), an AAA+ ATPase family member that functions in a wide range of cellular processes, including chromatin remodeling and transcriptional regulation.

9. Therefore, Dot1a and Af9 as aldosterone-downregulated targets are negative regulators of endothelin-1 transcription in vitro and in vivo, and may be considered as new potential therapeutic targets of kidney injury in diabetes.

10. It was concluded that +78/+92 of the epithelial Na+ channel alpha-subunit represents the primary Af9 binding site involved in recruiting Dot1a to repress basal and aldosterone-sensitive Na+ channel alpha-subunit transcription.

11. PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras(G12D) acute myeloid leukemia.

12. The role of polycomb repressive complex 2 (PRC2) function in leukemia development and progression, is reported.

13. Data show that the minimal 90-amino acid AF9 fragment in MLL-AF9 retains an ability to form higher order complexes with AF4*P-TEFb and with DOT1.

14. Dot1l, an H3K79 methyltransferase, is required for both initiation and maintenance of MLL-Af9-induced leukemogenesis in vitro and in vivo.

15. Af9/Mllt3 interferes with Tbr1 expression through epigenetic modification of histone H3K79 during development of the cerebral cortex

16. A shift in AF9 from the nucleus to the cytoplasm in response to Hsp90 interference leads to increased ENaCalpha expression. This is accompanied by a decrease in AF9 occupancy at the ENaCalpha promoter.

17. Af9 gene is required for normal embryogenesis in mice by controlling pattern formation, apparently via control of Hox gene regulation

18. Dot1a-AF9 modulates histone H3 Lys-79 methylation at the ENaCalpha promoter and represses ENaCalpha transcription in an aldosterone-sensitive manner

19. Af9 is a physiologic target of Sgk1, and Sgk1 negatively regulates the Dot1a-Af9 repressor complex that controls transcription of ENaCalpha and likely other aldosterone-induced genes.

20. Overlapping expression of Af9 with Af4/Aff1 and Fmr2/Aff2, two genes that are also related to neurodevelopmental diseases, as well as with the highly homologous Enl.